1. Field of the Invention
The present invention relates to a population of precursor/progenitor cells, particularly enriched with multipotent embryonic stem cell-like mesenchymal common progenitor cells (MCPCs), and method for enriching the same.
2. Description of Related Art
In regenerative medicine, to identify a source of stem cells of high safety and efficacy is the first step of the development of bio materials for repairing and renewing damaged and defective tissues. Human embryonic stem cells (hESCs) can remain undifferentiated, if cultured under appropriate conditions, and begin to spontaneously differentiate into various types of cells, which is a good indication that a culture of embryonic stem cells is a source for producing various types of cells. However, it is not an efficient way because to control the differentiation of embryonic stem cells is required (see: Stem Cells: Scientific Progress and Future Research Directions. Department of Health and Human Services. Jun. 2001.).
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types. MSCs have been isolated from placenta, adipose tissue, lung, bone marrow, dental pulp, and blood. Cell types that MSCs have been shown to differentiate into in vitro or in vivo osteoblasts, chondrocytes, myocytes, adipocytes, and beta-pancreatic islets cells. MSCs were found to be rare in bone marrow, representing ˜1 in 10,000 nucleated cells. Although not immortal, they have the ability to expand manyfold in culture while retaining their growth and multilineage potential. Pittenger et al. (Science 284, 143 (1999)) discloses that isolated mesenchymal (stem) cells were uniformly positive for SH2, SH3, CD29, CD44, CD71, CD90, CD106, CD120a, CD124, and many other surface proteins, while the mesenchymal cells were negative for other markers of the hematopoietic lineage, including the lipopolysaccharide receptors CD14, CD34, and the leukocyte common antigen CD45. MSCs are identified by the expression of many molecules including CD44 and CD105 and are negative for the hematopoietic markers CD34, CD45, and CD14.
It was reported that amniotic mesenchymal stromal cells and human chorionic mesenchymal stromal cells could be isolated from placenta. The surface antigen expression of these cells is given in Table A below, showing that they cannot express CD45, CD34, CD14 and HLA-DR (Parolini et al., Stem Cells 26: 300-311, 2008).
TABLE ASpecific antigen expression at passages 2-4 for amnioticmesenchymal stromal cells and human chorionic mesenchymal stromal cellsPositive (≧95%)Negative (≦2%)CD90 CD45CD73 CD34CD105CD14HLA-DR
Caplice (U.S. Pat. No. 7,790,453 B2) taught blood-derived, adult smooth muscle progenitor cells which were positive for CD34. However, the smooth muscle progenitor cells disclosed by Caplice are not characterized as mesenchymal stromal stem/progenitor cells and said progenitor cells have limited differentiation potential.
Lucas et al. (U.S. Pat. No. 7,259,011 B2) taught isolated human pluripotent adult stem cells (PPASCs) expressing CD13, CD34, CD56, and CD117. The PPASCs according to Lucas et al. did not express CD10, CD14, and stage specific embryonic antigen SSEA2. The PPASCs are not characterized as mesenchymal stromal stem/progenitor cells, either.
Hariri (U.S. Pat. No. 7,468,276 B2) taught isolated human placental stem cells that are OCT4+ and CD34+. The human placental stem cells disclosed by Hariri were SSEA3− and SSEA4−. The human placental stem cells of Hariri were not characterized as mesenchymal stromal stem/progenitor cells.
Edinger et al. (US 2008/0206343 A1) discloses non-adherent, CD34+CD45− stem cells isolated from placenta. The placental stem cells according to Edinger et al. are non-adherent, and thus were not mesenchymal.
For tissue engineering, an enriched population of multipotent stem cells that are juvenile and prolonged self-renewal are desired.